Peripheral circadian clocks are diversely affected by adrenalectomy

<p>Glucocorticoids are considered to synchronize the rhythmicity of clock genes in peripheral tissues; however, the role of circadian variations of endogenous glucocorticoids is not well defined. In the present study, we examined whether peripheral circadian clocks were impaired by adrenalectomy. To achieve this, we tested the circadian rhythmicity of core clock genes (<i>Bmal1, Per1-3, Cry1, RevErbα, Rora</i>), clock-output genes (<i>Dbp, E4bp4</i>) and a glucocorticoid- and clock-controlled gene (<i>Gilz</i>) in liver, jejunum, kidney cortex, splenocytes and visceral adipose tissue (VAT). Adrenalectomy did not affect the phase of clock gene rhythms but distinctly modulated clock gene mRNA levels, and this effect was partially tissue-dependent. Adrenalectomy had a significant inhibitory effect on the level of <i>Per1</i> mRNA in VAT, liver and jejunum, but not in kidney and splenocytes. Similarly, adrenalectomy down-regulated mRNA levels of <i>Per2</i> in splenocytes and VAT, <i>Per3</i> in jejunum, <i>RevErbα</i> in VAT and <i>Dbp</i> in VAT, kidney and splenocytes, whereas the mRNA amounts of <i>Per1</i> and <i>Per2</i> in kidney and <i>Per3</i> in VAT and splenocytes were up-regulated. On the other hand, adrenalectomy had minimal effects on <i>Rora</i> and <i>E4bp4</i> mRNAs. Adrenalectomy also resulted in decreased level of <i>Gilz</i> mRNA but did not alter the phase of its diurnal rhythm. Collectively, these findings suggest that adrenalectomy alters the mRNA levels of core clock genes and clock-output genes in peripheral organs and may cause tissue-specific modulations of their circadian profiles, which are reflected in changes of the amplitudes but not phases. Thus, the circulating corticosteroids are necessary for maintaining the high-amplitude rhythmicity of the peripheral clocks in a tissue-specific manner.</p>